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Abstract:

Novel, crosslinked polymers using biomass derived materials, such as
aldaric acids and derivatives, are provided. The polymers can be used as
hydrogels and in antimicrobial compositions.

Claims:

1. A hydrogel composition comprising: (1) water, and (2) a crosslinked
polymer, the crosslinked polymer comprising: A) a linear, branched or
cyclic polymeric backbone comprising repeat units that comprise one or
more groups selected from: hydrocarbylene groups selected from one or
more aliphatic, aromatic, linear, branched, or cyclic groups;
heteroatoms; and carbonyl groups; and B) one or more crosslinking units
that include at least one aldaroyl structural unit of Formula I:
##STR00019## where n is 1-6; wherein the hydrocarbylene groups and
heteroatoms of the repeat units are optionally substituted with
substituents that comprise one or more of C1-C30 hydrocarbylene
groups, heteroatoms, and carbonyl carbon groups, and wherein the
hydrocarbylene groups of the substituents are aliphatic or aromatic,
linear, branched, or cyclic, or combinations thereof.

3. The hydrogel composition of claim 1 wherein the substituents on the
hydrocarbylene groups and heteroatoms of the repeat units of the
crosslinked polymer comprise one or more of: --X, --O(Z), --N(ZZ'),
--N+(ZZ'Z''), --C(═O)OZ, --C(═O)X, --C(═O)NZZ',
--C═N═O, --O--, --N(Z)--, --N+(ZZ')--, --C(═O)N(Z)--,
--C(═O)O--, --C(═O)--, --OC(═O)O--, --OC(═O)N(Z)--,
--N(Z)C(═O)N(Z')--, --C(═O)NH(CH2)pNH2, --Si(ZZ')O--,
--(OCH2CH2)mOH, or --(OSi(ZZ'))nOH, and salts thereof, wherein X is a
halogen, Z, Z', and Z'' are independently hydrogen or C1-C22 alkyl,
substituted alkyl, aryl, or substituted aryl, and wherein m is 1 to 50, n
is 1 to 100, and p is 1 to 12.

4. The hydrogel composition of claim 3 wherein the repeat units of the
crosslinked polymer comprise aliphatic hydrocarbylene groups having
substituents comprising one or more of C1-C22 aminoalkyl
groups. --C(═O)OZ, --C(═O)X, --C(═O)NZZ', or
--C(═O)NH(CH2)pNH2, and salts thereof.

5. The hydrogel composition of claim 1 wherein at least one repeat unit
of the crosslinked polymer is an azahydrocarbylene or salt thereof,
comprising a nitrogen atom having one or more terminal aminoalkyl groups
or salts thereof as substituents.

6. The hydrogel composition of claim 1 wherein at least one repeat unit
of the crosslinked polymer contains one or more substituents comprising
one or more of C1-C22 aminoalkyl groups, optionally substituted
with alkyl or aldaroyl groups, or a salt thereof.

8. The hydrogel composition of claim 1 wherein the aldaroyl moiety in the
crosslinking unit is glucaroyl, galactaroyl, mannaroyl, xylaroyl, or
tartaroyl.

9. The hydrogel composition of claim 1 wherein the crosslinking unit
comprises one or more groups selected from groups having Formulae II,
III, IV, and V ##STR00020## wherein Q is --O-- or --NH--, or a salt
thereof, and R1, R2, R3 and R4 are aliphatic or
aromatic hydrocarbylene groups, linear, branched or cyclic, optionally
substituted, and optionally containing --O--, --Si(ZZ')O--, --(C═O)--
or --NZ-- linkages, where Z and Z' are independently hydrogen, alkyl,
substituted alkyl, alkaryl, substituted alkaryl, aryl, or substituted
aryl; and wherein the group having Formulae II, III, IV, or V is directly
attached to the polymer backbone.

11. The hydrogel composition of claim 1 wherein about 0.1% to about 100%
of the polymer backbone repeat units are connected to a crosslinking
unit.

12. The hydrogel composition of claim 11 wherein about 1% to about 30% of
the polymer backbone repeat units are connected to a crosslinking unit.

13. A hydrogel composition comprising: (a) water and (b) a crosslinked
polymer prepared by a process comprising contacting a crosslinking agent
with a substrate polymer to form a crosslinked polymer; wherein the
crosslinking agent has Formula VI, VII or VIII: ##STR00021## wherein L
and L' independently contain a suitable functional group, and n=1-6,
m=0-4, and p=1-4; and the substrate polymer comprises: A) a linear,
branched or cyclic polymeric backbone comprising repeat units that
comprise one or more of hydrocarbylene groups, heteroatoms, and carbonyl
carbon groups; wherein the hydrocarbylene are aliphatic or aromatic,
linear, branched, or cyclic, or combinations thereof; and wherein the
hydrocarbylene groups and heteroatoms of the repeat units are optionally
substituted with substituents that comprise one or more of
C1-C30 hydrocarbylene groups, heteroatoms, and carbonyl carbon
groups, wherein the hydrocarbylene groups of the substituents are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof; and B) reactive pendant groups attached to the polymeric
backbone, the pendant groups being of the formula -G or --R-G, wherein G
is a nucleophile or electrophile; wherein R is independently linear,
cyclic, or branched alkylene, arylene, or alkarylene groups of 1-22
carbon atoms, optionally substituted with alkyl, aryl, hydroxy, amino,
carbonyl, ester, amide, alkoxy, nitrile or halogen, and optionally
containing --O--, --Si(ZZ')O--, --(C═O)-- or --NZ-- linkages, where Z
and Z' are independently hydrogen, alkyl, substituted alkyl, alkaryl,
substituted alkaryl, aryl, or substituted aryl.

14. The hydrogel composition of claim 13 wherein the suitable functional
group of the crosslinked polymer is derived from an amine, hydroxyl,
carboxylic acid, ester, urethane, urea, amide, or isocyanate; and G is an
epoxide, isocyanate, benzylic halide, amine, acid halide, ester, or
amide.

16. The hydrogel composition of claim 13 wherein L and L' are
independently selected from optionally substituted --NHR'', --OH, and
--C(═O)OR''; and G is selected from --NH2, --C(═O)Cl,
--C(═O)OR'', or --C(═O)NH--R''--NH2, wherein R'' is
independently hydrogen or an optionally substituted hydrocarbyl or
hydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3.

17. The hydrogel composition of claim 13 wherein less than 100% of the
reactive pendant groups are derivatized to be substantially unreactive to
the crosslinking agent, wherein the derivatization is performed either
before, during or after contact of the crosslinker with the polymer
substrate.

18. The hydrogel composition of claim 13 wherein the reactive pendant
groups are derivatized before the contacting of the crosslinker with the
polymer substrate.

25. The hydrogel composition of claim 13 wherein the repeat units of the
substrate polymer comprise aliphatic hydrocarbylene groups with one or
more substituents comprising one or more of aminoalkyl groups,
--C(═O)OZ, --C(═O)X, --C(═O)NZZ', or
--C(═O)NH(CH2)nNH2, or salts thereof, where X is
halogen, Z and Z' are independently hydrogen, C1-C22 alkyl,
substituted alkyl, aryl, or substituted aryl, and n=1-12.

26. The hydrogel composition of claim 13 wherein substituents on the
repeat units are one or more of --X, --O(Z), --N(ZZ'), --N+(ZZ'Z''),
--C(═O)OZ, --C(═O)X, --C(═O)NZZ', --C═N═O, --O--,
--N(Z)--, --N+(ZZ')--, --C(═O)N(Z)--, --C(═O)O--,
--C(═O)--, --OC(═O)O--, --OC(═O)N(Z)--,
--N(Z)C(═O)N(Z')--, --C(═O)NH(CH2)pNH2,
--Si(ZZ')O--, --(OCH2CH2)mOH, or --(OSi(ZZ'))nOH, or
salts thereof, wherein X is a halogen, Z, Z', and Z'' are independently
hydrogen or C1-C22 optionally substituted alkyl or aryl, and
wherein m is 1 to 50, n is 1 to 100, and p is 1 to 12.

27. The hydrogel composition of claim 13 wherein the repeat units contain
substituents comprising one or more of C1-C22 aminoalkyl
groups, optionally substituted with alkyl or aldaroyl groups, or salts
thereof.

28. The hydrogel composition of claim 13 wherein at least one repeat unit
is an azahydrocarbylene or salt thereof, comprising a nitrogen atom
having one or more terminal aminoalkyl groups or salts thereof as
substituents.

36. The hydrogel composition of claim 32 wherein about 0.0005 to about
0.5 molar equivalents of crosslinking agent are used per reactive pendant
group.

37. The hydrogel composition of claim 32 wherein about from about 0.005
to about 0.5 molar equivalents of crosslinking agent are used per
reactive pendant group.

38. The hydrogel composition of claim 32 wherein 0.01 to 0.25 molar
equivalents of the reactive pendant groups are derivatized.

Description:

[0001] This application is a Divisional of U.S. application Ser. No.
11/064,191, now granted, filed on Feb. 23, 2005.

FIELD OF INVENTION

[0002] The invention is directed to the preparation of novel, crosslinked
polymers using biomass derived materials, such as aldaric acids and
derivatives. These polymers can be used as hydrogels.

BACKGROUND

[0003] The concept of using biomass-derived materials to produce other
useful products has been explored since man first used plant materials
and animal fur to make clothing and tools. Biomass derived materials have
also been used for centuries as adhesives, solvents, lighting materials,
fuels, inks/paints/coatings, colorants, perfumes and medicines. Recently,
people have begun to explore the possibility of using "refined biomass"
as starting materials for chemical conversions leading to novel high
value-in-use products. Over the past two decades, the cost of renewable
biomass materials has decreased to a point where many are competitive
with those derived from petroleum. In addition, many materials that
cannot be produced simply from petroleum feedstocks are potentially
available from biomass or refined biomass. Many of these unique, highly
functionalized, molecules would be expected to yield products unlike any
produced by current chemical processes. "Refined biomass" is purified
chemical compounds derived from the first or second round of plant
biomass processing. Examples of such materials include cellulose,
sucrose, glucose, fructose, sorbitol, erythritol, and various vegetable
oils.

[0004] A particularly useful class of refined biomass is that of aldaric
acids. Aldaric acids, also known as saccharic acids, are diacids derived
from naturally occurring sugars. When aldoses are exposed to strong
oxidizing agents, such as nitric acid, both the aldehydic carbon atom and
the carbon bearing the primary hydroxyl group are oxidized to carboxyl
groups. An attractive feature of these aldaric acids includes the use of
very inexpensive sugar based feedstocks, which provide low raw material
costs and ultimately could provide low polymer costs if the proper
oxidation processes are found. Also, the high functional density of these
aldaric acids provide unique, high value opportunities, which are
completely unattainable at a reasonable cost from petroleum based
feedstocks.

[0005] Hydrogels (hydrated gel) are polymers that contain water-swellable,
three-dimensional networks of macromolecules held together by covalent or
noncovalent (e.g., ionic or hydrogen bonded) crosslinks. Upon placement
in an aqueous environment, these networks swell to the extent allowed by
the degree of crosslinking. They are used in many fields such as medical
applications, personal care formulations, coatings, and surfactants.

[0006] U.S. Pat. No. 5,496,545 discloses crosslinked polyallylamine and
polyethyleneimine. The crosslinking agents disclosed include
epichlorohydrin, diepoxides, diisocyanates,
α,ω-dihaloalkanes, diacrylates, bisacrylamides, succinyl
chloride, and dimethyl succinate. The present invention provides new
crosslinked polymers that can function as hydrogels. The polymers
comprise crosslinking moieties that can be derived from biomass sources.

SUMMARY OF THE INVENTION

[0007] One aspect of the present invention is a crosslinked polymer
comprising:

[0008] a linear, branched or cyclic polymeric backbone comprising repeat
units that comprise one or more of each of: hydrocarbylene groups,
heteroatoms, and carbonyl carbon groups; wherein the hydrocarbylene
groups are aliphatic or aromatic, linear, branched, or cyclic, and can
include combinations of aliphatic, aromatic, linear, branched and/or
cyclic hydrocarbylene groups; and

[0009] one or more crosslinking units containing at least one aldaroyl
structural unit of Formula I:

##STR00001##

[0010] where n is 1-6.

[0011] The hydrocarbylene groups and heteroatoms of the repeat units are
optionally substituted with substituents that comprise one or more of
C1-C30 hydrocarbylene groups, heteroatoms, and carbonyl carbon
groups, wherein the hydrocarbylene groups of the substituents are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof.

[0012] Preferably the crosslinking units are one or more of Formulae II,
III, IV, and V:

[0014] and wherein Formulae II, III, IV, and V are directly attached to
the polymer backbone.

[0015] Another aspect of the present invention is a crosslinked polymer
prepared by a process comprising contacting a crosslinking agent with a
substrate polymer to form a crosslinked polymer, wherein the crosslinking
agent is one or more of Formulae VI, VII and VIII:

[0018] a linear, branched or cyclic polymeric backbone comprised of repeat
units that comprise one or more of hydrocarbylene groups, heteroatoms,
and carbonyl carbon groups

[0019] wherein the hydrocarbylene groups are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof; and

[0020] reactive pendant groups attached to the polymeric backbone, the
pendant groups being of the formula -G or --R-G.

[0021] wherein G is a
nucleophile or electrophile;

[0022] wherein R is independently linear,
cyclic, or branched alkylene, arylene, or alkarylene groups of 1-22
carbon atoms, optionally substituted with alkyl, aryl, hydroxy, amino,
carbonyl, ester, amide, alkoxy, nitrile or halogen, and optionally
containing --O--, --Si(ZZ')O--, --(C═O)-- or --NZ-- linkages, where Z
and Z' are independently hydrogen, alkyl, substituted alkyl, alkaryl,
substituted alkaryl, aryl, or substituted aryl. The hydrocarbylene groups
and heteroatoms of the repeat units are optionally substituted with
substituents that comprise one or more of C1-C30 hydrocarbylene
groups, heteroatoms, and carbonyl carbon groups. The hydrocarbylene
groups of the substituents can be aliphatic or aromatic, linear,
branched, or cyclic, or combinations thereof. Preferably, L and L' are
derived from an amine, hydroxyl, carboxylic acid, ester, urethane, urea,
amide, or isocyanate; and G is an epoxide, isocyanate, benzylic halide,
amine, acid halide, ester, or amide. Also preferably L and L' are
selected from optionally substituted --NHR'', --OR'', and
hydrocarbylene-C(═O)OR'' and G is selected from --NH2,
--C(═O)Cl, --C(═O)OR'', or --C(═O)NH--R''--NH2; wherein
R'' is independently an optionally substituted hydrocarbyl or
hydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3. The optional
substituents on R'' can be any heteroatom-containing group that does not
participate directly in reactions between the substrate polymer and the
crosslinking agent; i.e., the substituent is preferably not displaced
during such reaction and does not form a covalent bond with the substrate
polymer. Groups attached to the polymer by reaction with G can contain
aza (--NZ--) or ether (--O--) linkages (e.g., G can be PEGylated). In one
embodiment of the process, less than 100% of the reactive pendant groups
are derivatized such that the derivatized pendant groups are
substantially unreactive to the crosslinking agent. "Substantially
unreactive", as used herein, means having a rate of reaction, e.g., with
the crosslinking agent, of about 20% or less of the rate of reaction of
an underivatized pendant group under the same conditions. The
derivatization can be performed before, during or after contact of the
crosslinking group with the polymer substrate. Preferably, the reactive
pendant groups are derivatized to contain an optionally substituted
aliphatic carbon chain with optional --(NZ)--, and --O-- linkages, where
Z is hydrogen, optionally substituted alkyl or optionally substituted
aryl.

[0023] In another embodiment, the crosslinking agent is derived from an
aldaric acid, aldarolactone, aldarodilactone, aldarolactone ester,
aldaric acid monoester, aldaric acid diester, or aldaramide, or salts
thereof, and the substrate polymer comprises polyallylamine,
polyallylamine hydrochloride, branched polyethyleneimine, branched
polyethyleneimine hydrochloride, poly(acryloyl chloride),
poly(methacryloyl chloride), poly[N-(ω-aminoalkyl)acrylamide],
polyglycosamine, carboxymethylchitosan, chitosan, chitosan hydrochloride,
or derivatives or salts thereof. By "derived from" is meant that the
crosslinking agent can be produced from a starting compound in about six
or fewer chemical reaction steps, and retains an aldaric structure
--C(═O)(CHOR)nC(═O)-- wherein R is H or a carbon-containing
group such as alkyl.

[0024] Preferably the crosslinking agent is one or more of the Formulae
IX, X, XI, and XII:

[0028] The polymers and processes can be used to form compositions,
emulsifiers, thickeners, and personal care products comprising the
polymers. Examples of personal care products that can be made from the
polymers include skin and hair conditioners. In some embodiments, the
polymers or products made therefrom are antimicrobial.

[0029] Other aspects of the invention include a method of cleaning and
smoothing human skin and a method of conditioning hair comprising the
application of an effective amount of the polymers of the invention. Also
included are methods for killing, inhibiting, or preventing the growth of
at least one microbe, the method comprising contacting the microbe with
an effective amount of a crosslinked polymer according to the invention,
a method of reducing microbial population on a surface comprising
contacting a surface with an effective amount of the crosslinked polymer
for a time sufficient to reduce the microbial population on the surface,
an antimicrobial substrate comprising a crosslinked polymer according to
the invention that is bound to or incorporated into the substrate, and
articles comprising such antimicrobial substrates.

[0030] These and other aspects of the present invention will be apparent
to one skilled in the art, in view of the following description and the
appended claims.

DETAILED DESCRIPTION

[0031] The following definitions may be used for the interpretation of the
present specification and the claims:

[0034] "Aryl" means a group defined as a monovalent radical formed
conceptually by removal of a hydrogen atom from a hydrocarbon that is
structurally composed entirely of one or more benzene rings. Examples of
aryl groups include benzene, biphenyl, terphenyl, naphthalene, phenyl
naphthalene, and naphthylbenzene.

[0035] "Alkaryl" means an alkylated aryl group; that is, an aryl group as
defined above that is substituted with an alkyl group.

[0036] By "hydrocarbylene," "alkylene," "arylene," or "alkarylene" is
meant the divalent form of the corresponding group.

[0037] "Substituted" means that a group contains one or more substituent
groups, or "substituents," that do not cause the compound to be unstable
or unsuitable for the use or reaction intended. Unless otherwise
specified herein, when a group is stated to be "substituted" or
"optionally substituted," substituent groups that can be present include
carboxyl, carboxamido (including primary, secondary or tertiary
carboxamido), acylamino, alkoxycarbonylamino, sulfonylamino, cyano,
alkoxy, alkoxycarbonyl, acyloxy, fluoro, chloro, bromo, iodo, amino
(including primary, secondary and tertiary amino), hydroxy, alkenyl, oxo,
imino, hydroxyimino, hydrocarbyloxyimino, wherein the hydrocarbyl group
can be aliphatic, aryl or a combination of the two, trihydrocarbylsilyl,
wherein each hydrocarbyl group can be independently alkyl or aryl,
trihydrocarbylsiloxy, wherein each hydrocarbyl group can be independently
alkyl or aryl, nitro, nitroso, hydrocarbylthio, wherein the hydrocarbyl
group can be aliphatic, aryl or a combination of the two,
hydrocarbylsulfonyl, wherein the hydrocarbyl group can be aliphatic, aryl
or a combination of the two, hydrocarbylsulfinyl, wherein the hydrocarbyl
group can be aliphatic, aryl or a combination of the two,
hydrocarbyloxysulfonyl, wherein the hydrocarbyl group can be aliphatic,
aryl or a combination of the two, sulfonamido (including primary,
secondary and tertiary sulfonamido), sulfonyl, dihydrocarbylphosphino,
wherein each hydrocarbyl group can be independently alkyl or aryl,
dihydrocarbyloxyphosphino, wherein each hydrocarbyl group can be
independently alkyl or aryl, hydrocarbylphosphonyl, wherein the
hydrocarbyl group can be aliphatic, aryl or a combination of the two,
hydrocarbyloxyphosphonyl, wherein the hydrocarbyl group can be aliphatic,
aryl or a combination of the two, phosphonamido (including primary,
secondary and tertiary phosphonamido), and salts of the aforementioned.

[0038] The present invention is directed to a crosslinked polymer
comprising a polymeric backbone and one or more crosslinking units
containing at least one aldaroyl unit.

[0041] wherein the hydrocarbylene groups are aliphatic or aromatic,
linear, branched, or cyclic, or combinations thereof; and

[0042] B) one or more crosslinking units containing at least one aldaroyl
structural unit of Formula I:

##STR00006##

[0043] where n is 1-6.

[0044] The hydrocarbylene groups and heteroatoms of the repeat units are
optionally substituted with substituents that comprise one or more of
C1-C30 hydrocarbylene groups, heteroatoms, and carbonyl carbon
groups, wherein the hydrocarbylene groups of the substituents are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof.

[0045] The crosslinker shown in Formula I is attached to the polymer
backbone via the available valences at either end of the structural unit.
They are attached either directly with no other atoms between the
structure of Formula I and the backbone of the polymer, or indirectly
with other atoms or structural groups between Formula I and the polymer
backbone. For example, in one embodiment shown below, the crosslinking
unit (in which n=4) is indirectly attached to the polyethylene backbone
via the --NH--CH2--C(═O)--NH--CH2-- structural unit:

##STR00007##

[0046] Aldaric acids are diacids derived from naturally occurring sugars.
When aldoses are exposed to strong oxidizing agents, such as nitric acid,
both the aldehydic carbon atom and the carbon bearing the primary
hydroxyl group are oxidized to carboxyl groups. This family of diacids is
known as aldaric acids (or saccharic acids). An aldarolactone has one
carboxylic acid lactonized; the aldarodilactone has both lactonized. As
illustration, the aldaric acid derivatives starting from D-glucose are
shown below.

##STR00008##

[0047] Any stereoisomer or mixture of stereoisomers can be used in the
compositions and processes disclosed herein. The aldaric acid derivative
can be glucaric acid or galactaric acid, or their derivatives such as,
for example, glucarolactone, glucarodilactone, galactarolactone, and
dimethyl galactarate.

[0049] The repeat units of the crosslinked polymer preferably comprise
aliphatic hydrocarbylene groups with substituents comprising one or more
of aminoalkyl groups, --C(═O)OZ, --C(═O)X, --C(═O)NZZ', or
--C(═O)NH(CH2)pNH2, or salts thereof. The repeat units
are also preferably azahydrocarbylenes or salts thereof, with one or more
terminal aminoalkyl groups or salts thereof as substituents on the
nitrogen of the azahydrocarbylene repeat unit. Also preferably the repeat
units contain substituents comprising one or more of C1-C22
aminoalkyl groups, optionally substituted with alkyl or aldaroyl groups
or salts thereof. The aldaroyl moiety in the crosslinking unit is
preferably glucaroyl, galactaroyl, mannaroyl, xylaroyl, or tartaroyl.

[0050] In one embodiment, the crosslinked polymer is a derivative of
polyallylamine, polyallylamine hydrochloride, branched polyethyleneimine,
branched polyethyleneimine hydrochloride, poly(acryloyl chloride),
poly(methacryloyl chloride), poly[N-(ω-aminoalkyl)acrylamide],
polyglycosamine, carboxymethylchitosan, chitosan, chitosan hydrochloride,
or a derivative or salt thereof. For example, polymers having amine
groups can have some of the amine groups alkylated, acylated, sulfonated,
or reacted to form imines or aminals. Also, they can be in one or more
salt forms or partial salt forms, e.g., polyallyamine hydrochloride can
be converted to its p-toluenesulfonic acid or acetic acid salt. Polymers
with acyl chloride groups can be partially reacted with a monofunctional
alcohol or amine to form ester or amide side chains. Such derivatives
retain the backbone structure and preferably some of the reactive side
chain structure as the original polymer from which the derivative is
derived. The crosslinked polymer can additionally comprise one or more of
the crosslinking units of Formulae II, III, IV, or V:

[0057] The R3 moieties,
--[CH(CH3)CH2O]xCH2C(Z')(CH2[OCH2CH(CH3)]y--)CH2[OCH2CH(CH3)]z-- and
--[CH(CH3)CH2O]xCH2CH([OCH2CH(CH3)]y)C-
H2[OCH2CH(CH3)]z--, are trivalent and therefore can
react to form crosslinked structures. Other polyalkylene,
polyalkyleneoxide, and polyalkylenearyl structures can be trivalent,
tetravalent, or higher multivalent. Therefore, when R3 is
multivalent, the polymer of the instant invention can exist in a
multivalent crosslinked structure with the empty valences on the
polyalkyleneoxide being endcapped by available functionalities such as
amines.

[0058] Preferably about 0.1% to about 100% of the polymer backbone repeat
units are connected to a crosslinking unit. More preferably about 1% to
about 30% of the polymer backbone repeat units are connected to a
crosslinking unit.

[0059] Also provided according to the invention are crosslinked polymers
prepared by a process comprising contacting a crosslinking agent with a
substrate polymer to form a crosslinked polymer, wherein the crosslinking
agent is one or more of Formulae VI, VII and VIII:

[0061] The substrate polymer used in the instant process comprises a
linear, branched or cyclic polymeric backbone. The backbone contains
repeat units that comprise one or more of hydrocarbylene groups,
heteroatoms, and carbonyl carbon groups. The hydrocarbylene groups are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof. The hydrocarbylene groups and heteroatoms of the repeat units
are optionally substituted with substituents that comprise one or more of
C1-C30 hydrocarbylene groups, heteroatoms, and carbonyl carbon
groups, wherein the hydrocarbylene groups of the substituents are
aliphatic or aromatic, linear, branched, or cyclic, or combinations
thereof.

[0063] The substituents on the repeat units are preferably one or more of
--X, --O(Z), --N(ZZ'), --N+(ZZ'Z''), --C(═O)OZ, --C(═O)X,
--C(═O)NZZ', --C═N═O, --O--, --N(Z)--, --N+(ZZ')--,
--C(═O)N(Z)--, --C(═O)O--, --C(═O)--, --OC(═O)O--,
--OC(═O)N(Z)--, --N(Z)C(═O)N(Z')--,
--C(═O)NH(CH2)pNH2, --Si(ZZ')O--,
--(OCH2CH2)mOH, or --(OSi(ZZ'))nOH, or salts thereof,
where X is a halogen, Z, Z', and Z'' are independently hydrogen,
C1-C22 optionally substituted alkyl, or C1-C22
optionally substituted aryl, and where m is 1 to 50, n is 1 to 100, and p
is 1 to 12. More preferably, the substituents comprise one or more of
C1-C22 aminoalkyl groups, optionally substituted with alkyl or
aldaroyl, or a salt thereof. The repeat units preferably comprise
aliphatic hydrocarbylene groups with substituents comprising one or more
of aminoalkyl groups, --C(═O)OZ, --C(═O)X, --C(═O)NZZ', or
--C(═O)NH(CH2)nNH2, or salts thereof, where X is
halogen, Z and Z' are independently hydrogen, C1-C22 alkyl,
substituted alkyl, aryl, or substituted aryl, and n=1-12.

[0064] The repeat unit can be an azahydrocarbylene or salt thereof with
one or more terminal amino groups or salts thereof as substituents on the
N of the azahydrocarbylene repeat unit.

[0067] The terms, "electrophile" and "nucleophile," are well known to
those skilled in the art, and can be broadly defined as reactive chemical
moieties that act as electron acceptors or electron donors respectively.
Preferably, G is an epoxide, isocyanate, benzylic halide, amine, acid
halide, ester, or amide; more preferably G is --NH2, --C(═O)Cl,
--C(═O)OR'' or --C(═O)NH--R''--NH2 wherein R'' is
independently hydrogen or an optionally substituted hydrocarbyl or
hydrocarbylene. Most preferably G is --NH2.

[0068] L and L' are defined as containing a suitable functional group. A
suitable functional group is herein defined as a functional group that
readily forms a covalent bond with the reactive pendant group. The
functional group employed depends upon the synthetic method used to make
the crosslinked polymer. The functional group can contain heteroatoms
such as O, N, S, and/or can be derived from a functional group such as an
amine, hydroxyl, carboxylic acid, ester, urethane, urea, amide, or
isocyanate. Particularly useful functional groups are those that contain
a --NH-- group, a --C(═O)O-- group, a --O-- group, or salts thereof.
Preferably, the suitable functional group is derived from an amine,
hydroxyl, carboxylic acid, ester, urethane, urea, amide, or isocyanate.
More preferably L and L' are independently selected from --Y--R, wherein
Y is O, NH, or S and R is alkyl, substituted alkyl, alkaryl, substituted
alkaryl, aryl, or substituted aryl. Also more preferably L and L' are
independently selected from optionally substituted --NHR'', --OR'', and
hydrocarbylene-C(═O)OR''; wherein R'' is an optionally substituted
hydrocarbylene, and wherein n=2-4, m=0-1, and p=2-3.

[0069] As illustration, a crosslinker that is capped with a carboxylic
acid as the suitable functional group would be expected to react readily
with available amine pendant groups on the polymeric backbone. A
crosslinker end-capped with a hydroxyl group or an amine as a functional
group would not be expected to react with the pendant amine functionality
of the polymeric backbone. However, if the subject polymer backbone had a
carboxylic acid or an isocyanate as pendant functionality, then a
crosslinker capped with an amine or a hydroxyl functional group could
react with the pendant group of the polymeric backbone.

[0070] In another embodiment, less than 100%, preferably up to about 50%,
and more preferably up to about 20% of the reactive pendant groups are
derivatized so that they are unreactive to the crosslinking agent. The
derivatization can be performed by contacting the reactive pendant groups
with a derivatizing reagent before, during or after contact of the
crosslinker with the substrate polymer. Preferably, the reactive pendant
groups are derivatized before the contact of the crosslinker with the
polymer substrate. The reactive pendant groups can be derivatized to
contain an optionally substituted aliphatic carbon chain with optional
--(NZ)--, and --O-linkages, where Z is hydrogen, optionally substituted
alkyl or optionally substituted aryl. Preferably, the reactive pendant
groups are derivatized to contain a linear or branched alkyl group of
1-22 carbon atoms, optionally substituted with --O-- linkages, and
optionally substituted with --NH2, halogen, hydroxyl, or carbonyl
groups, or salts thereof, more preferably a C1-C22 alkyl group,
most preferably a C2-C18 unsubstituted alkyl group.

[0079] Examples of polyoxaalkyleneamines that can be used include to those
based on Jeffamine® polyether amines (Huntsman LLC, Salt Lake City,
Utah). Examples of polytetramethylene glycols that can be used include
those based on Terethane® polytetramethyleneetherglycol (E. I. DuPont
de Nemours, Wilmington, Del.).

[0080] In some embodiments, about 0.0005 to about 0.5 molar equivalents of
crosslinking agent per reactive pendant group can be used in the process.
Preferably, from about 0.005 to about 0.5 molar equivalents of
crosslinking agent are used per reactive pendant group, and more
preferably about 0.01 to 0.25 molar equivalents per reactive pendant
group.

[0081] The processes can be run at any suitable temperature but preferably
at about 20° C. to about 100° C. The processes can be
carried out in a polymer melt, but are preferably carried out in the
presence of a solvent. The choice of solvent is not critical provided the
solvent is not detrimental to reactant or product. Preferred solvents
include water, dimethylformamide, dimethylformamide LiCl,
dimethylacetamide, dimethylacetamide LiCl, ethanol, and methanol.

[0082] The polymers disclosed herein are suitable for use as hydrogels.
Hydrogels (hydrated gels) are herein defined as materials that absorb
large quantities of liquid, i.e., greater than 2 mass equivalents of
liquid. They are usually water-swellable, three-dimensional networks of
macromolecules held together by covalent or noncovalent crosslinks. When
placed in aqueous solution, the networks swell to the extent allowed by
the degree of crosslinking.

[0083] Hydrogels are useful in many applications, such as medical
products, personal care formulations, exfoliants, humectants,
surfactants, thickeners, anti-irritants, antimicrobials, lubricants,
emulsifiers, delivery agents, coatings, and surfactants. In some
embodiments the hydrogels are conducting. The polymers can be modified to
introduce a wide range of properties to make them more suitable in such
applications. Additionally, divalent crosslinking agents as disclosed
herein can be used as water-soluble chain extenders for polyurethanes,
and hydroxylated block or comb copolymers made with the processes
described herein can be used as pigment dispersants. When used as
co-polymers or modifiers to other polymeric materials, the polymers can
impart moisture wicking improvements, dyeability, and/or flame resistance
to the other materials.

[0084] As used herein, the term "antimicrobial" means killing, or
preventing or inhibiting the growth of, microorganisms, including
bacteria and fungi. "Growth inhibition" means reduced rate of growth of a
population of microorganisms. "Growth prevention" means that growth is
stopped.

[0085] Polymers described herein are also suitable for use in cosmetic
products.

[0086] Also provided are methods for cleaning and/or smoothing human skin
comprising the application of an effective amount of the polymers
described herein, and methods of conditioning hair comprising the
application of an effective amount of the polymers described herein.

[0087] As used herein, "cosmetic products" are products intended for
increasing the appeal, visually and/or olfactorily, of the human body.
Likewise, "personal care products" are products intended for cleaning,
smoothing or otherwise improving the health, feel, or well-being of the
outside of the human body. These definitions of cosmetic and personal
care products at least partially overlap since many products provide
functions in both categories. Examples of cosmetic products are: perfumes
and like products known as "eau de toilette" and "eau de parfum," hand
and body lotions, skin tonics, shaving products, bath and shower
products, deodorant and antiperspirant products, hair care products such
as shampoos and hair conditioners, and mouth and dental care products.
Such products are well known in the art. Thus, examples of skin care
products are described in "Harry's Cosmeticology," R. G. Harry, 6th
edition, Leonard Hill Books (1973), Chapters 5-13, 18 and 35; examples of
deodorants and antiperspirants are described in C. Fox, cosmetics and
Toiletries 100 (December 1985), pp 27-41; examples of hair care products
are described "Harry's Cosmeticololgy," vide supra, chapters 25-27;
examples of dental care products are described in M. Pader, Oral Hygiene:
Products and Practice, Marcel Dekker, New York (1988).

[0088] For use in the personal care field, the polymers can be modified to
enhance moisture retention, lubricity, static control, curl retention,
sheen, and/or "body" in hair-care related products. For skin care
products could the polymers can be used to make exfoliants (for example,
as α-hydroxy acid replacements), humectants, surfactants,
thickeners, anti-irritants, antimicrobials, lubricants, emulsifiers, and
delivery agents. The polymers can be used to make topical antimicrobial
substances or barriers, or as additives to inhibit microbial growth in a
separate formulation, or may impart residual antimicrobial activity. Such
residual antimicrobial activity can be imparted to a surface, for
example, by depositing the polymer onto the surface or by covalently or
otherwise attaching the polymer to the surface. Examples of surfaces to
which the polymers can be applied include steel, and plastic, although
substantially any surface can be treated by application of the polymers.
Antimicrobial products containing the polymers can be applied to animal
skin, including human skin.

[0089] Skin conditioning agents as herein defined include astringents,
which tighten skin; exfoliants, which remove exterior skin cells:
emollients, which help maintain a smooth, soft, pliable feel and
appearance; humectants, which increase the water content of the top layer
of skin; occlusives, which retard evaporation of water from the skin's
surface; and miscellaneous compounds that enhance the feel and/or
appearance of dry or damaged skin or reduce flaking and restore
suppleness. Skin conditioning agents are well known in the art, and are
disclosed, for example, in Green et al. WO 0107009, and are available
commercially from various sources. Examples of skin conditioning agents
include alpha-hydroxy acids, beta-hydroxy acids, polyols, hyaluronic
acid, D,L-panthenol, polysalicylates, vitamin A palmitate, vitamin E
acetate, glycerin, sorbitol, silicones, silicone derivatives, lanolin,
natural oils, and triglyceride esters.

[0090] The skin care, hair care, and hair coloring compositions made from
the polymers can also contain one or more conventional cosmetic or
dermatological additives or adjuvants, such as, for example, fillers,
surfactants, thixotropic agents, antioxidants, preserving agents, dyes,
pigments, fragrances, thickeners, vitamins, hormones, moisturizers, UV
absorbing sunscreens, wetting agents, cationic, anionic, nonionic or
amphoteric polymers, and hair coloring active substances. Such adjuvants
are well known in the field of cosmetics and are disclosed, for example,
in "Harry's Cosmeticology." 8th edition, Martin Rieger, ed.,
Chemical Publishing, New York (2000).

[0091] The polymers can also function as surface disinfectants, or as
ingredients in a formulation designed to function as a surface
disinfectant.

[0092] For use in medical applications, the polymers can act as coatings
that retain moisture, lubricate, conduct electricity, facilitate
sustained release of therapeutic agents, absorb undesirable materials
that accumulate in the area of an implant, or act as local antimicrobial
agents. The materials of the current invention can be used as components
of polymeric medical adhesives (or anti-adhesives), as monomeric
crosslinkers, and as components of adhesives that can be deactivated to
prevent bandages from creating or enlarging sores on chronically bandaged
areas. In the area of medical devices, the polymers can be used as
biocompatible agents to attach antimicrobial, anti-inflammatory, or
anti-proliferative agents to the surface of catheters, stents, or other
medical implants. Sustained release can be accomplished by slow diffusion
of at least one biologically active agent out of the polymeric hydrogel
matrix. Sustained release can further be facilitated by slow hydrolysis
of the crosslink bonds.

[0097] DSC and TGA studies of all polymers were conducted on 5-10 mg
samples run at 10° C./min under nitrogen. Sample temperatures
spanned ranges beginning as low as -100° C. to as high as
300° C., depending on polymer character and stability. Samples
were generally cooled after the first heat cycle and a second heat cycle
was then conducted. Generally, polymer DSC results reported are second
heat results to eliminate artifacts of thermal history variations.

Swell Factor

[0098] Into a pre-dried, tared, 150 mL coarse fritted filter funnel was
added about 1 g of polymer. The stem of the funnel was sealed with a
rubber stopper. The funnel was placed on a filter flask and about 100 mL
of distilled water at about 22° C. is added to the funnel. The
contents were stirred, if necessary, to fully disperse the water and
polymer. The contents were then left undisturbed for 15 minutes. The
rubber stopper was then removed from the stem of the funnel, and suction
was applied to the funnel for 5 minutes. The stem and underside of the
funnel were then rinsed with ethanol to remove any remaining water
droplets and suction was then continued for an additional 5 minutes. Any
remaining water droplets were wiped off the funnel with a paper towel.
The funnel and contents were then weighed to determine the weight of
water retained by the polymer.

[0099] Solubilities were generally determined using 0.01 g of test
material in 10 mL of test solvent. The vials containing the samples were
constantly agitated via a shaker tray at room temperature for anywhere
between 24 hours and 4 weeks. Solubility was determined by visual
inspection to determine sample homogeneity. Any variance in density
gradient, or refractive index was taken as indicating insolubility.
Samples deemed to be insoluble were shaken at room temperature for at
least 1 week, and in many cases were shaken for 2 weeks or more. A wide
range of common solvent types was generally used to allow a broad range
of polarity and solvent parameters to come into play.

Film Properties

[0100] Film properties were determined on 0.25 inch×2 inch samples
cut from larger films spread onto glass with a blade applicator.
Generally, films had thicknesses of 5 mil or less. Film properties
reported represent an average of at least five measurements for each
sample.

[0101] The reactions depicted in the following Examples are meant to be
illustrative only and not representative of exact structures.

Examples 1-28

[0102] Polymers were prepared by first dissolving polyallylamine
hydrochloride of ˜60,000 molecular weight in water. To that
solution was added enough sodium hydroxide to just neutralize the
equivalent amount of ammonium hydrochloride functions as would be used by
the added GDL. To the partially neutralized polyallylamine hydrochloride
was added a water solution of GDL at room temperature. The reaction was
substantially over in a matter of minutes. A representative
polymerization with GDL is shown below.

[0103] The crosslinking was performed using various compounds as described
below in a representative reaction with GDL. When another compound was
used in the in the crosslinking reaction along with the GDL, such as 9DA,
they were both added simultaneously. Into a 250-mL 3-necked round bottom
flask equipped with a heating mantle, reflux condenser, nitrogen inlet,
and overhead stirrer was added 20 mL of water, 2.80 g (0.030 equivalent,
60,000 MW) of polyallylamine HCl, and 0.26 g (0.0066 mol) of sodium
hydroxide. This mixture was stirred at room temperature until a
homogeneous solution was achieved (˜10 minutes). At this point, a
homogeneous solution prepared from 10 mL of water and 0.57 g (0.0033 mol)
of GDL was slowly poured at room temperature into the solution containing
the polyallylamine HCl. Within 1 to 2 minutes, gel had formed. The gel
was then allowed to stir for ˜2 hours at room temperature, after
which time it was removed from the flask. The gel was then washed 3 times
with 100 mL aliquots of methanol followed by THF. The gel was then dried
in a vacuum oven at 80° C. to yield 2.79 g (89.1%) of a granular
white hydrogel polymer. The results are shown in Table 1. The %
crosslinking shown in Table 1 is a theoretical calculation of the % of
total amine nitrogens (from the polyallylamine hydrochloride) tied up in
the crosslinking process with the aldaric acid. The calculation was based
on the total weight of polyallylamine hydrochloride used (molar
equivalents of allylamine) and the total molar equivalents of the GDL
added to the process. Total final crosslinking was not measured but is
assumed since the polymer gelled and became insoluble, although NMR
indicated that conversion was less than 100%.

[0104] When only 5-15% of the ammonium groups were allowed to react with
GDL, a very viscous water solution resulted that could be cast into a
film. The resulting films were brittle, but less so than the starting
polyallylamine hydrochloride homopolymer. As more ammonium groups reacted
with GDL, gels eventually formed. Highly swellable hydrogels (with swell
ratios as high as 90) were readily formed when ˜22% of the ammonium
hydrochloride equivalents were neutralized and GDL was added in an
equivalent amount (˜11% since both ends of the molecule are assumed
to react). The gels were optically clear and colorless.

[0105] The data in Tables 1 and 2 show some of the properties that can be
obtained in the polymers by varying the ingredients used in making them.

[0106] Into a 2000-mL 3-necked flask equipped with a heating mantle,
reflux condenser, nitrogen inlet, and overhead stirrer was added 525 mL
of water, 70 g of polyallylamine hydrochloride (0.749 mole equivalent of
amine), and 2.24 g (0.056 mol) of sodium hydroxide. After these
ingredients dissolved. 17.08 g (0.056 mol) of 1-bromohexadecane was
added. The reaction mixture was heated at reflux for 5 hours. Afterward,
the reaction mixture was cooled to room temperature and stirred
overnight. An additional 5.60 g (0.140 mol) of sodium hydroxide was added
to the mixture. After the sodium hydroxide dissolved, 12.18 g (0.070 mol)
of GDL dissolved in 175 mL of water was added to the reaction mixture.
Almost immediately a gel formed. The gelled mixture was then gently
heated at 50° C. for about 7 hours. The gel was filtered, washed
3× with methanol, and then washed 3× with THF. It was then
put into a vacuum oven set at 80° C. for at 24 hours to dry the
polymer. The pale yellow polymer (58.85 g, 60.5%) exhibited a swell ratio
of 7.9.

Example 30A

Synthesis of Polyallylamine Crosslinked with Diethyl Tartrate

[0107] The preparation was conducted under nitrogen atmosphere with
oven-dried glassware. Polyallylamine hydrochloride (MW ca. 60,000, 0.876
g, 9.36 mmol) was weighed into a 20-mL scintillation vial equipped with a
magnetic stirbar, and water (2 mL) was added. Dropwise addition of an
aqueous solution (1.0 mL) of sodium hydroxide (0.113 g, 2.83 mmol) to the
solution resulted in a viscous solution. A solution of diethyl L-tartrate
(0.240 mL, 1.40 mmol) in water (1.0 mL) was added and the resulting
solution was stirred at ambient temperatures for 38 hours. The gelled
reaction mixture was washed with methanol (160 mL) to remove sodium
chloride. Vacuum-drying gave a white solid (0.86 g, 93% yield) that
exhibited a swell ratio of 112.6 (determined after swollen gel was
subjected to 6 hours of dynamic suction followed by ˜28 hours of
static suction).

Example 30B

Synthesis of Polyallylamine Crosslinked with Diethyl Tartrate

[0108] Poly(allylamine hydrochloride), Mw 60,000 (42.04 g, 0.4493
mole of amine groups) was dissolved overnight in 155 mL of water in a
3-neck 500-mL round-bottom flask equipped with a magnetic stir bar. A
solution of 5.392 g (0.1348 mole) of sodium hydroxide in 25 mL of water
was added dropwise over a period of 10 minutes, using 2 mL of water to
complete the transfer. To the resulting pale yellow syrup was added with
stirring a solution of 13.897 g (67.40 mmoles) of diethyl L-tartrate in
10 mL of water, using 2 mL of water to complete the transfer. The
reaction was allowed to proceed for 4 days, during which the mixture
gelled and the magnetic stir bar seized. The reaction mixture was
combined with 250 mL of methanol to precipitate out the product. The
resulting gummy solid was separated from the liquid and triturated in a
blender with 8 successive 250-mL portions of methanol, decanting the
methanol each time. The resulting solid was ground and dried under vacuum
to give 38.47 g (86% yield) of hydrogel that exhibited a swell factor of
224.

Example 31

Synthesis of Polyallylamine Crosslinked with GDL

##STR00013##

[0110] The preparation was conducted in a drybox with oven-dried
glassware. Polyallylamine hydrochloride (MW ca. 60,000, 6.88 g, 73.5
mmol) was weighed into a 500-mL round-bottom flask equipped with a
magnetic stirbar. Methanol (285 mL) was added and the solution was
treated with neat triethylamine (12.3 mL, 88.3 mmol) followed by dropwise
addition of a solution of GDL (0.13 g, 0.74 mmol) in methanol (10 mL).
The resulting solution was stirred at ambient temperature for four days.
Most of the reaction solvent was decanted, and the remaining reaction
mixture was filtered and vacuum-dried to give a white solid (1.00 g, 23%
yield) that exhibited a swell ratio of 22.8. When the swell test was
repeated, allowing 19 hours for the gel to swell followed by 2 hours of
dynamic suction and 9 hours of static suction, the swell ratio was 22.4.
After 14 hours' exposure to ambient atmosphere, the sample retained 19.9
times its own weight in water.

Example 32A

Synthesis of Polyallylamine Crosslinked with
N,N'-Bis(ethoxycarbonylmethyl)-D-glucaramide

##STR00014##

[0112] Preparation was conducted in a drybox with oven-dried glassware.
Polyallylamine hydrochloride (MW ca. 60,000, 6.55 g, 70.0 mmol) was
weighed into a 500-mL round-bottom flask equipped with a magnetic
stirbar. Methanol (270 mL) was added and the solution was treated with
neat triethylamine (11.7 mL, 84.0 mmol) followed by a slurry of
N,N'-bis(methoxycarbonylmethyl)-D-glucaramide (0.25 g, 0.69 mmol) in
methanol (20 mL). The resulting solution was stirred at ambient
temperature for four days. The reaction solvent was removed under vacuum,
and the oily solid was washed repeatedly with methanol (180 mL). Addition
of pentane (50 mL) to a methanol slurry (ca. 20 mL volume) produced a
solid that was filtered and then vacuum-dried to give a white solid (2.39
g, 57% yield) that exhibited a swell ratio (after 29 minutes of suction)
of 62.8. When the swell test was repeated, allowing 16 hours for the gel
to swell followed by 34 minutes of suction, the swell ratio was 118.9.
After 23 hours' exposure to ambient atmosphere, the sample retained 108.6
times its own weight in water.

Example 32B

Synthesis of Polyallylamine Crosslinked with
N,N'-Bis(ethoxycarbonylmethyl)-D-glucaramide

[0113] To 23.03 g (0.2463 mole of amine groups) of poly(allylamine
hydrochloride), Mw 60,000, in 950 mL of dry methanol in a 2-L
round-bottom flask under nitrogen were added 41.2 mL (0.296 mole) of
triethylamine over 30 minutes. A slurry of
N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide in a total of 65 mL of dry
methanol was then added. The mixture was stirred at ambient temperature
for 5 days and then concentrated under reduced pressure to about 150 mL.
The resulting solid was separated from the methanol, washed repeatedly
with methanol and then dried under vacuum to give 12.92 g (88% yield) of
hydrogel that exhibited a swell factor of 125.

Example 33

##STR00015##

[0115] Polyallylamine hydrochloride (MW ca. 60,000, 2.84 g, 30.4 mmol) was
weighed into 100-mL round-bottom flask equipped with a magnetic stirbar.
Water (16 mL) was added and the solution was treated with an aqueous (4
mL) solution of sodium hydroxide (0.27 g, 6.67 mmol) followed by a
solution of GDL (0.58 g. 3.34 mmol) in water (10 mL). The reaction
solution was stirred overnight at ambient temperature resulting in a
gel-like mixture. The gel was washed with four 50-mL portions of methanol
and then vacuum-dried to give a white solid (2.26 g, 69% yield) that
exhibited a swell ratio (after 2 hours of suction) of 186.5. After 3
additional days' exposure to static suction, the sample retained 67.9
times its own weight in water. When the swell test was repeated with the
same sample, allowing 5 hours for the gel to swell followed by 2 hours of
dynamic suction and 24 hours of static suction, the swell ratio was
206.0. After 3 and 8 days' additional exposure to static suction, the
sample retained 173.8 and 65.5 times its own weight in water,
respectively.

Example 34

##STR00016##

[0117] Preparation was conducted under nitrogen atmosphere with oven-dried
glassware. Polyallylamine hydrochloride (MW ca. 60,000, 1.01 g, 10.8
mmol) was weighed into a 20-mL scintillation vial equipped with a
magnetic stirbar, and water (2 mL) was added. Dropwise addition to the
slurry of an aqueous solution (1.0 mL) of sodium hydroxide (0.033 g, 0.83
mmol) resulted in a viscous solution. A solution of
N,N'-bis(methoxycarbonylmethyl)-D-glucaramide (0.14 g, 0.41 mmol) in
water (1.5 mL) was added, and the resulting solution was stirred at
ambient temperature for 45 hours. Solvent was removed under vacuum from
the gelled reaction mixture, and the solid was washed with methanol (125
mL) to remove sodium chloride. Vacuum-drying gave a white solid (0.98 g,
89% yield) that exhibited a swell ratio (after 5 minutes of dynamic
suction and 45 minutes of static suction) of 105.8. After 2 days'
exposure to ambient atmosphere, the sample retained 96.5 times its own
weight in water. When the swell test was repeated with the same sample,
allowing 4.5 hours for the gel to swell followed by 5 hours of dynamic
suction and 14 hours of static suction, the swell ratio was 197.6. After
6 days' exposure to ambient atmosphere, the sample retained 167.8 times
its own weight in water.

Example 35

##STR00017##

[0118] Polyethylenimine (Mn=ca. 10,000, Mw=ca. 25,000, Aldrich
408727, 0.74 g, 17.2 mmol) was weighed into a 20-mL scintillation vial
equipped with a magnetic stirbar, and methanol (4.5 mL) was added.
Concentrated hydrochloric acid (0.72 mL, 8.65 mmol) was added to the
reaction solution dropwise over ca. one minute and the mixture was
stirred at ambient temperature for 3 hours. A solution of GDL (0.15 g,
0.862 mmol) in methanol (1 mL) was added dropwise over ca. one minute to
the reaction solution. The reaction mixture began to gel after 3 hours,
but stirring was continued for 24 hours. The solvent was removed under
vacuum and the solid was vacuum-dried to give a yellow solid (ca. 0.2 g)
that exhibited a swell ratio (after 1 hour of static suction) of 24.1.
After 5 days' exposure to ambient atmosphere, the sample retained 9.2
times its own weight in water. When the swell test was repeated with the
same sample, allowing 7.5 hours for the gel to swell followed by 35
minutes of dynamic suction, the swell ratio was 36.6. After 1 day's
exposure to ambient atmosphere, the sample retained 34.2 times its own
weight in water.

Example 36

##STR00018##

[0120] Polyethylenimine (Mn=ca. 10,000, Mw=ca. 25,000, Aldrich
408727, 0.67 g, 15.6 mmol) was weighed into a 20-mL scintillation vial
equipped with a magnetic stirbar, and water (2.5 mL) was added.
Concentrated hydrochloric acid (0.65 mL) was added dropwise to the
solution followed by solid N,N'-bis(methoxycarbonylmethyl)-D-glucaramide
(0.14 g, 0.39 mmol) and water (1 mL). The reaction solution was stirred
for 5 days at ambient temperature. The solvent was then removed under
vacuum, and the solid was vacuum-dried to give a colorless solid that
exhibited a swell ratio (after 50 minutes of dynamic suction and 15
minutes of static suction) of 17.6. When the swell test was repeated with
the same sample, allowing 15 hours for the gel to swell followed by 2.25
hours of suction, the swell ratio was 25.5. After five days' exposure to
ambient atmosphere, the sample retained 22.8 times its own weight in
water.

Example 37

Biocidal Activity of Crosslinked Hydrogels

[0121] Antimicrobial activity was determined by a standard micro-shake
flask test. Bacterial cultures were inoculated into TSB (Trypticase Soy
Broth) and incubated at 37° C. overnight for 20+/-2 hours. The
following day, the concentration of bacteria was adjusted to
-1.0×105 cfu/mL (cfu=colony forming unit) by dilution with 0.6
mM phosphate buffer. Diluted bacterial culture (2.5 mL) was then
transferred into culture plate wells containing 2.5 mL of hydrogel
(˜50 mg of solid dispersed in 2.5 mL of 0.6 mM phosphate buffer) or
just 2.5 mL of 0.6 mM phosphate buffer (control). The culture plates were
incubated at room temperature on a platform shaker with constant shaking
motion. Three 100-μL aliquots were periodically removed from each well
and serially diluted with 0.6 mM phosphate buffer. Undiluted and diluted
samples from each well were plated onto duplicate TSA (trypticase soy
agar) plates, and incubated at 37° C. for 20±2 hrs. After
incubation, the number of bacterial colonies on each plate was counted
using a Q-count instrument or equivalent counting method. The colony
count was averaged and normalized by correcting for the dilution factor
and reported as the number of colony forming units (cfu) per mL. Log
reduction (log rdxn)=(mean log10 density of microbes in flasks of
untreated control samples)-(mean log10 density of microbes in flasks
of treated samples).

[0123] Three hydrogel samples were tested for antimicrobial activity:
Sample A was prepared as in Example 29. Sample B was prepared in the
manner of Example 30A. Sample C was prepared as in Example 31. Results
are in Table 4.

[0124] A crosslinked hydrogel was prepared in the following manner: 28.0 g
(0.30 equiv of polyallylamine hydrochloride was dissolved in 200 mL of
water along with 2.4 g (0.06 mol) of sodium hydroxide. To that solution
was added a solution of 5.2 g (0.030 mol) of GDL and 2.9 g (0.015 mol) of
Jeffamine® EDR-192 dissolved in 100 mL of water. The mixture was then
heated to 50° C. Within 1 hour, a gelled product had formed. The
gel was left to "cure" overnight at room temperature. It was then
filtered and washed 3 times with MeOH/THF. The remaining polymer was then
dried in a vacuum oven at 80° C. to yield 20.63 g (61%) of a white
granular material. The polymer exhibited a swell ratio of 81.

[0125] An emulsion was prepared using 2.0 g of the polymer prepared above,
17.0 g of octyl palmitate, and 148 mL of water. These ingredients were
added to a 250-mL beaker and emulsified using a Silverson Lab Mixer
equipped with a rotor-stator square-holed blade running at 5,000 rpm for
5 min. A thick, creamy white emulsion was prepared. After 8 months'
storage in a jar at room temperature, separation of the emulsion was
negligible.

Example 39

Preparation of Crosslinked Polymer Using Poly(Methacryloyl Chloride), GDL,
and Ethylenediamine

[0126] Into a 250-mL 3-necked round-bottom flask equipped with a heating
mantle, reflux condenser, nitrogen inlet, and overhead stirrer was added
a 25 mL of dioxane containing 6.25 g (0.598 equivalent) of
poly(methacryloyl chloride) (Polysciences, Inc., Warrington, Pa.). To
this solution was added 3.5 g (0.0150 mol) of
N,N'-bis(2-aminoethyl)-D-glucaramide (prepared by reacting 10 equivalents
of ethylenediamine with GDL in DMAC at 50° C. and isolating the
product as a white precipitate). The mixture was stirred and heated at
50° C. over a period of 21 hours. During this time, a slight color
change from brown to yellow was noted; however, it did not appear that
the diaminodiamide was ever fully solubilized in the dioxane solvent. The
resulting product was poured into THF, filtered, and washed 3 times with
THF to yield 2.65 g (27%) of a light tan solid material; Tg1
49.67° C.; Tg2 64.14° C.; Tdec 175°
C.--onset; ηinh (HFIP) insol.

Example 40

Synthesis of Chitosan Crosslinked with GDL

[0127] Chitosan (Primex TM-656, MW ca. 79,000.95% deacetylated, 0.79 g,
4.90 mmol) was weighed into a 20-mL scintillation vial equipped with a
magnetic stirbar. Water (11.5 mL) was added, and the mixture was stirred
for 15 minutes at ambient temperature. A solution of hydrochloric acid
(37%, 0.29 mL, 3.45 mmol) in water (1.5 mL) was added dropwise, and the
resulting viscous light yellow mixture was stirred for 15 minutes at
ambient temperature. A freshly prepared solution of GDL (0.09 g, 5.40
mmol) in water (1.5 mL) was added dropwise, and the reaction mixture was
stirred for 38 hours at ambient temperature, resulting in a tan-colored
homogeneous gel-like mixture. Approximately 5 mL of the solvent was
removed under vacuum and the reaction mixture was transferred to a
round-bottom flask with 15 mL of tetrahydrofuran. The resulting
precipitate was washed with four 30-mL portions of tetrahydrofuran then
vacuum-dried to give a white solid (0.75 g) that had a swell ratio of 3.

Example 41

Hard Surface Disinfection by Crosslinked Hydrogels

[0128] Tests were performed by Consumer Product Testing Company,
Fairfield, N.J. following Association of Official Analytical Chemists
(AOAC) Use Dilution test methods 955.14 and 955.15.

[0129] Hydrogel A was prepared by reacting poly(allylamine hydrochloride),
Mw 60,000, with 0.15 mole equivalent (relative to amine groups) of
diethyl L-tartrate according to Example 30B to give a polymer nominally
having 30% of its amine groups crosslinked. Hydrogel B was prepared by
reacting poly(allylamine hydrochloride), Mw 60,000, with 0.01 mole
equivalent (relative to amine groups) of
N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32B to
give a polymer nominally having 2% of its amine groups crosslinked. Each
hydrogel was dispersed in deionized water, hydrogel A at 0.5 wt % (w/v)
and hydrogel B at 1 wt % (w/v).

[0130] Type 304 stainless steel penicylinders (8 mm OD, 6 mm ID, 10 mm L)
were soaked overnight in 1 N sodium hydroxide, washed with water until
the rinse water was neutral to phenolphthalein, and autoclaved in 0.1%
w/v aqueous asparagine solution. The sterile penicylinders were drained
and transferred aseptically into a 48-hour culture broth (1 mL per
cylinder) of Staphylococcus aureus (ATCC#6538) or Salmonella choleraesuis
(ATCC#10708). After being immersed in culture broth for 15 minutes, the
penicylinders were drained and transferred by sterile hook into a sterile
glass petri dish lined with sterile filter paper so that the cylinders
stood on end without touching one another. The penicylinders were dried
at 37° C. for 40 minutes.

[0131] For each hydrogel tested, 10 penicylinders inoculated with a given
test organism were immersed individually for 10 minutes at 20° C.
in 10 mL of aqueous hydrogel dispersion. Each penicylinder was then
removed from the hydrogel dispersion, drained, and deposited into a
primary culture tube containing 10 mL of Letheen broth and incubated at
37° C. After 30 minutes, each penicylinder was transferred into
secondary culture tube containing 10 mL of Letheen broth, and both
primary and secondary culture tubes were incubated at 37° C. for
48 hours, after which they were examined for microbial growth as
evidenced by turbidity.

[0132] Neutralization of each antimicrobial hydrogel by double serial
subculture was shown to be effective by inoculating tubes showing no
growth with low levels of test organism. Viability of test organisms was
demonstrated by incubating inoculated penicylinders in deionized water
instead of a hydrogel suspension.

[0133] Results in Table 5 demonstrate that hydrogel B is bactericidal
against Staphylococcus aureus. While it is also active against Salmonella
choleraesuis, hydrogel B does not completely eradicate viable Salmonella
choleraesuis under the conditions employed.

[0134] Skin creams were formulated by mixing ingredients in the amounts
listed in Table 6. The crosslinked hydrogel used was made according to
Example 30B.

[0135] Ingredients of Phase 1 were combined and heated to 77° C.
Ingredients of Phase 2 were combined and heated to 77° C. While
Phase 1 was kept at 77° C. and vigorously agitated by an overhead
stirrer, Phase 2 was added to Phase 1. After 15 minutes of vigorous
agitation at 77° C., triethanolamine was added to the mixture.
After the mixture had been vigorously agitated at 77° C. for an
additional 15 to 25 minutes, external heating was discontinued, and the
vigorously agitated mixture was allowed to cool. When the temperature of
the mixture reached 37 to 38° C., Dow Corning 200® fluid
dimethicone was added, the speed of agitation was reduced, and the
mixture was allowed to cool to room temperature.

[0136] Ten grams of each skin cream formulation were supplemented with 500
μL of trypticase soy broth, mixed in by hand, to promote bacterial
growth. Each skin cream sample was then inoculated with 100 μL of a
1:10 dilution of an overnight culture of Pseudomonas aeruginosa and 100
μL of a 1:10 dilution of an overnight culture of Staphylococcus
aureus, yielding a bacterial load of approximately 1×106 cfu/g
for each organism (cfu=colony forming unit). Periodically, each
inoculated skin cream was sampled with a 10-μL loop, which was then
streaked onto a trypticase soy agar (TSA) plate. Plates were incubated at
37° C. for 24 hours and then examined for bacterial growth.

[0137] Results in Table 7 show that bacteria persisted in the unpreserved
control sample, A, but not in the sample containing crosslinked hydrogel,
B.

[0138] Microbiological tests were performed by Consumer Product Testing
Company, Fairfield, N.J. according to the United States Pharmacopoeia
(USP), 24th Edition, <51> Antimicrobial Effectiveness Testing.

[0139] Hydrogel A was prepared by reacting poly(allylamine hydrochloride),
Mw 60,000, with 0.15 mole equivalent (relative to amine groups) of
diethyl L-tartrate according to Example 30B to give a polymer nominally
having 30% of its amine groups crosslinked. Hydrogel B was prepared by
reacting poly(allylamine hydrochloride), Mw 60,000, with 0.01 mole
equivalent (relative to amine groups) of
N,N'-bis(ethoxycarbonylmethyl)-o-glucaramide according to Example 32B to
give a polymer nominally having 2% of its amine groups crosslinked.

[0140] Skin creams were formulated by mixing ingredients in the amounts
listed in Table 8. Ingredients of Phase 1 were combined and heated to
77° C. Ingredients of Phase 2 were combined and heated to
77° C. While Phase 1 was kept at 77° C. and vigorously
agitated by an overhead stirrer, Phase 2 was added to Phase 1. After 15
minutes of vigorous agitation at 77° C., triethanolamine was added
to the mixture. After the mixture had been vigorously agitated at
77° C. for an additional 15 to 25 minutes, external heating was
discontinued, and the vigorously agitated mixture was allowed to cool.
When the temperature of the mixture reached 37 to 38° C., Dow
Corning 200® fluid dimethicone was added, the speed of agitation was
reduced, and the mixture was allowed to cool to room temperature.

[0141] The microbial tests described below were performed by Consumer
Product Testing Company, Fairfield, N.J. Twenty-gram portions of each
skin cream formulation were aseptically transferred into sterile glass
containers and inoculated with 100 μL of a 1×108 cfu/mL
culture of Staphylococcus aureus (ATCC#6538), Escherichia coli
(ATCC#8739), Pseudomonas aeruginosa (ATCC#9027), Candida albicans
(ATCC#10231) or Aspergillus niger (ATCC#16404), yielding a microbial load
between 1×105 and 1×106 cfu/g. Inoculated samples
were incubated at 20 to 25° C. protected from light. Periodically,
samples of each inoculated skin cream were serially diluted tenfold, and
microbial counts were determined by the pour plate method, using
trypticase soy agar (TSA) plates incubated at 20 to 25° C. for 3
days for bacteria and Sabouraud dextrose agar (SDA) plates incubated at
20 to 25° C. for 5 days for the fungi.

[0142] Results in Table 9 demonstrate that the hydrogels increase the rate
of kill of gram positive (S. aureus) and gram negative (E. coli, P.
aeruginosa) bacteria and yeast (C. albicans) in a skin cream formulation.
No activity against mold (A. niger) was demonstrated by the two hydrogel
compositions tested.

[0143] Hydrogel A was prepared by reacting poly(allylamine hydrochloride),
Mw 60,000, with 0.15 mole equivalent (relative to amine groups) of
diethyl L-tartrate according to Example 30B to give a polymer nominally
having 30% of its amine groups crosslinked. Hydrogel B was prepared by
reacting poly(allylamine hydrochloride), Mw 60,000, with 0.01 mole
equivalent (relative to amine groups) of
N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32B to
give a polymer nominally having 2% of its amine groups crosslinked. Each
hydrogel was dispersed in deionized water, hydrogel A at 0.5 wt % (w/v)
and hydrogel B at 0.8 wt % (w/v).

[0144] The Repeat Insult Patch Test was performed by Consumer Product
Testing Company, Fairfield, N.J. The fifty-two subjects completing this
test included 12 men, age 32 to 68 years, and 40 women, age 22 to 79
years. Subjects had no visible skin disease, were in good health, were
not pregnant or nursing, were not under a doctor's care or taking
medication that would influence the outcome of the study, and had not
used a topical or systemic steroid or antihistamine for at least seven
days prior to beginning the study.

[0145] Approximately 0.2 mL of each hydrogel dispersion, or an amount
sufficient to cover the contact surface, was applied to the
3/4''×3/4'' absorbent pad of an adhesive dressing. The dressing was
then applied to a marked spot between the scapulae of each subject, thus
forming an occlusive patch. Patches were applied to the same site three
times a week (typically, Monday, Wednesday, and Friday) for three
consecutive weeks (total of 9 applications). Each patch was removed after
24 hours of contact. The site of application was examined and scored upon
removal of the first patch and again 24 hours after removal of the first
patch. Thereafter, the site of application was examined and scored 24 or
48 hours after the removal of each patch, usually just before application
of the subsequent patch. Thus, the application site on each subject was
examined 10 times during the Induction Phase. Approximately 2 weeks after
application of the final Induction patch, a Challenge patch was applied
to a virgin site adjacent to the original site, following the same
procedure as described above. The patch was removed 24 hours after
application, and the site was examined and scored. The Challenge site was
examined and scored again 48 hours after removal of the Challenge patch.

[0146] Each time an Induction or Challenge site was examined, it was
scored according to the following scale: 0=no visible skin reaction,
+=barely perceptible or spotty erythema, 1=mild erythema covering most of
the test site, 2=moderate erythema with possible presence of mild edema,
3=marked erythema with possible edema, and 4=severe erythema with
possible edema, vesiculation, bullae or ulceration. For both materials
tested, all scores (10 Induction and 2 Challenge for each of 52 subjects)
were 0. In addition, 5 subjects who began the study but discontinued for
various reasons not related to the test materials generated scores of
only 0 as well. Thus, hydrogel A and hydrogel B showed no dermal
irritation or allergic contact sensitization.

Example 44

Speed of Kill of Crosslinked Hydrogels

[0147] Hydrogel A was prepared by reacting poly(allylamine hydrochloride),
Mw 60,000, with 0.01 mole equivalent (relative to amine groups) of
N,N'-bis(ethoxycarbonylmethyl)-D-glucaramide according to Example 32A to
give a polymer nominally having 2% of its amine groups crosslinked.
Hydrogel B was prepared by reacting poly(allylamine hydrochloride),
Mw 60,000, with 0.15 mole equivalent (relative to amine groups) of
diethyl L-tartrate according to Example 30A to give a polymer nominally
having 30% of its amine groups crosslinked. Hydrogel C was prepared by
reacting poly(allylamine hydrochloride), Mw 60,000, with 0.25 mole
equivalent (relative to amine groups) of diethyl L-tartrate according to
Example 30, except using 0.900 g of poly(allylamine hydrochloride), 0.192
g of sodium hydroxide, and 0.412 mL of diethyl L-tartrate and allowing
the reaction to proceed for 88 hours before washing with methanol, to
give a polymer nominally having 50% of its amine groups crosslinked.

[0148] For each hydrogel, an exposure of E. coli to a 100 ppm loading was
effected by dispersing 5 mg of hydrogel in 25 mL of 0.6 mM phosphate
buffer, stirring overnight, and then adding 25 mL of a culture broth
(˜1.0×105 cfu/mL) of Escherichia coli ATCC#25922. After
15, 30, 60, 120, 180, and 240 minutes, aliquots of the test mixture were
removed and serially diluted 1:10 with TSB in a 96-well microtiter plate.
After incubating overnight at 37° C., each plate was scored for
microbial growth using a Most Probable Number (MPN) protocol, and log
reduction calculated as (mean log10 density of microbes in untreated
control samples)-(mean log10 MPN density of microbes in treated
samples).

[0149] Exposure of E. coli to a 10 ppm loading of each hydrogel was
effected similarly except using 1 mg of hydrogel in 50 mL of buffer and
adding 50 mL of a culture broth (˜1.0×105 cfu/mL) of
Escherichia coli ATCC#25922.

[0150] Results in Table 10 show that all three hydrogels eliminate viable
E. coli when present at 100 ppm. At 10 ppm loading, it becomes more
apparent that the speed of kill of hydrogel A is faster than that of
hydrogel B, which is faster than that of hydrogel C.